Summary of Issue 1 Transcript

Hi and welcome to the JNCI podcast, a production of the Journal of the National Cancer Institute. I’m Steve Graff, JNCI’s assistant news and media editor, and I’ll be taking you through the journal’s first issue of 2010.

In the first article of this issue, researchers make an argument for a cardio-oncology field because of the risks from chemotherapy to the cardiovascular system. Other studies include an assessment of lead time of selected ovarian cancer biomarkers, dermatologic infections in cancer patients treated with epidermal growth factor receptor inhibitor therapy, and the risk of heart disease and diabetes for patients on androgen deprivation therapy. In this issue’s last study, researchers looked at DC-SCRIPT and its prognostic value in breast cancer.

All that in more detail coming up next…..

According to a new review published online December 10, cardiologists and oncologists must work together in an attempt to avoid or prevent adverse cardiovascular effects in patients from certain chemotherapies, especially for those who may be at a higher risk for such effects.

With an aging population, it is highly probable that an increasing number of people may have both cancer and cardiovascular disease. Many chemotherapeutic and chemoprevention drugs affect the cardiovascular system, making cardiovascular side effects a new challenge in cancer therapy.

In a review of the literature, Adriana Albini, Chief of Oncology Research of the Clinical and Research Institute MultiMedica, Milan, Italy, and others from the Universities of Milan, Genova and Varese, summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk before patients are treated. They also stress the need to develop guidelines that include collateral effects on the cardiovascular system, as well as a new interdisciplinary field that could be termed “cardio-oncology.”

Identification of high-risk patients, by way of new biomarkers, for example, and imaging techniques will be a key strategy to reduce morbidity and mortality, according to the authors. Approaches include screening on entry into clinical trials for both cancer therapy and prevention, helping in choice of therapy, and use of agents that prevent cardiotoxicity. Finally, assessment of cardiotoxicity in phase I trials to develop new agents with less risk is of paramount importance.

According to a new study published online December 30, concentrations of the biomarkers CA125, human epididymis protein 4, and mesothelin began to rise 3 years before clinical diagnosis of ovarian cancer. However, the biomarkers became substantially elevated only in the last year prior to diagnosis. The stage of the cancer at the time of marker elevation is not known.

Most of these biomarkers have been identified as potential ovarian cancer biomarkers, but their behavior in the pre-diagnostic period, with the exception of CA125, has not been evaluated previously.

In this study, Garnet L. Anderson., of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, and colleagues analyzed stored serum samples from the Carotene and Retinol Efficacy Trial, a randomized, double-blind, placebo-controlled chemoprevention trial testing the effects of beta-carotene and retinol on lung cancer incidence among individuals at high risk for the disease. The researchers identified 34 patients who were diagnosed with ovarian cancer and had serum specimens available from the trial, as well as 70 matched control subjects.

Serum concentrations of CA125, human epididymis protein 4, and mesothelin began to increase slightly in cancer patients approximately 3 years before diagnosis but became substantially elevated only about a year before diagnosis.

These data suggest the presence of ovarian cancer up to 3 years before clinical diagnosis, but the likely lead time associated with these markers appears to be less than 1 year, according to the authors.

In an accompanying editorial, Patricia Hartge, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, Md., applauds the authors for taking the field one step closer to successful screening designs by showing that the levels of certain biomarkers do not increase early enough to be used for screening.

Patients who experience dermatologic toxic effects from epidermal growth factor receptor inhibitors have a high prevalence of skin and nail infections, according to a new study published online December 9.

These inhibitors, which are a new class of anticancer agents, are used against various cancers including lung, pancreatic, breast, head and neck, and colorectal cancers. Patients treated with these inhibitors frequently experience toxic effects such as eruptions of the face, dry, itchy skin and nail inflammation. These side effects affect quality of life, but the impact of these effects on the patients’ physical health, such as their increased susceptibility to cutaneous infections, has not been ascertained.

To examine this issue, Mario E. Lacouture., at the department of dermatology at Northwestern University in Chicago, and colleagues collected data on 221 patients who were treated in a referral clinic for dermatologic toxic effects of the inhibitors. They examined associations between patient characteristics and the development of these infections.

The researchers found that 38% of the 221 patients showed evidence of skin and nail infections, and 29% developed bacterial infections at sites previously affected by dermatologic toxic effects. About 23 % of the patients had cultures positive for Staphylococcus aureus, and 5.4 of the patients cultured positive for methicillin-resistant S. aureus, which could be resistant to many common antibiotics.

Men of all ages treated for prostate cancer with androgen deprivation therapy, specifically with gonadotropin-releasing hormone agonists have an increased risk of diabetes and cardiovascular disease, according to a new study published online December 7.

Previous studies indicate that older men who take androgen deprivation therapy for prostate cancer are at an increased risk for diabetes and cardiovascular disease, but the relationship between the two among men of all ages is unclear.

Nancy L. Keating, of the Division of General Internal Medicine, Department of Medicine, Brigham and Women’s Hospital in Boston, and colleagues conducted an observational study of almost 38,000 men of all ages who were diagnosed with local or regional prostate cancer in the Veterans Healthcare Administration from January 2001 through December 2004, with follow-up through December 2005.

Cox proportional hazards models were used to assess whether androgen deprivation therapy with the agonists, oral antiandrogens ( which are drugs that block the action of hormones), the combination of the two, or orchiectomy (which is removal of the testicles) were associated with diabetes, coronary heart disease, myocardial infarction, sudden cardiac death, or stroke, after adjustment for patient and tumor characteristics.

Treatment with these agonists was associated with statistically significant increased risks of incident diabetes.

“Additional research is needed to understand the effects of GnRH agonists for clinical settings where benefits have not yet been established, to identify populations of men at highest risk of complications associated with GnRH agonists, and to investigate strategies to prevent treatment-related morbidity,” the authors write.

In an accompanying editorial, Peter Albertsen, University of Connecticut Health Center in Farmington, said this study adds to the growing body of literature on androgen deprivation therapy. The researchers gave a glimpse into the extent of therapy side effects for contemporary patients, including men younger than 55 and older than 75 years, according to Albertsen.

DC-SCRIPT, or dendritic cell-specific transcript, is a key regulator of nuclear receptor activity that may have prognostic value in breast cancer, according to a new study published online December 14.

In this study, a team led by Gosse J. Adema, of the Department of Tumor Immunology, at the Radboud University Nijmegen Medical Centre, the Netherlands, and colleagues assessed the role of DC-SCRIPT as a co-regulator of nuclear receptors, including estrogen receptor, progesterone receptor-B, peroxisome proliferator–activated receptor gamma, and retinoic acid receptor alpha. Prognostic value was assessed in three independent cohorts of breast cancer patients.

The researchers found that DC-SCRIPT suppressed ER- and PR-mediated transcription in a ligand-dependent fashion, whereas it enhanced the activity of the other two receptors. Quantification of DC-SCRIPT mRNA expression in the three cohorts of patients revealed that this expression is an independent prognostic factor for breast cancer patients with ER– and/or PR–positive tumors, according to the authors.

In addition, they showed that breast tumors express lower levels of DC-SCRIPT mRNA than normal breast tissue and that breast tumor cell lines do not express it.

That’s it for this edition of the JNCI podcast. As always, find these studies online at jnci.oxfordjournals.org or listen to more podcasts at oxfordjournals.org/podcasts.

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